Deglycosylation as a Mechanism of Inducible Antibiotic Resistance Revealed Using a Global Relational Tree for One-Component Regulators
Deglycosylation as a Mechanism of Inducible Antibiotic Resistance Revealed Using a Global Relational Tree for One-Component Regulators
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DOI：
10.1016/j.chembiol.2012.11.011
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发表时间：
2013-02-21
影响因子：
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通讯作者：
Nodwell, Justin R.
中科院分区：
文献类型：
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作者：
Cuthbertson, Leslie;Ahn, Sang Kyun;Nodwell, Justin R.
与绝大多数小分子结合转录因子相互作用的配体是未知的，这是我们对细胞感觉感知的理解中的一个重大差距。TetR家族调节因子存在于大多数原核生物中，参与调控原核生物生命的方方面面，但目前仅有少数TFR被鉴定。我们报道了系统基因组学在TFRs同源配体鉴定中的应用。利用系统基因组学，我们确定了一种对抗生素kijAnimicin有反应的TFR，KijR。我们继续证明KijR抑制了一种基因kijX，该基因赋予了对kijAnimicin的耐药性。最后，我们证明了KijX通过水解糖残留物来灭活KijAnimicin。这是通过脱糖作用产生抗生素耐药性的证明。
The ligands that interact with the vast majority of small-molecule binding transcription factors are unknown, a significant gap in our understanding of sensory perception by cells. TetR-family regulators (TFRs) are found in most prokaryotes and are involved in regulating virtually every aspect of prokaryotic life however only a few TFRs have been characterized. We report the application of phylogenomics to the identification of cognate ligands for TFRs. Using phylogenomics we identify a TFR, KijR, that responds to the antibiotic kijanimicin. We go on to show that KijR represses a gene, kijX, which confers resistance to kijanimicin. Finally we show that KijX inactivates kijanimicin by the hydrolytic removal of sugar residues. This is a demonstration of antibiotic resistance by deglycosylation.